Variant chr2-61825319-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001201543.2(FAM161A):c.*1136G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000865 in 454,110 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00082 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00089 ( 0 hom. )

Consequence

FAM161A
NM_001201543.2 3_prime_UTR

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.993

Variant links:

Genes affected

FAM161A (HGNC:25808): (FAM161 centrosomal protein A) This gene belongs to the FAM161 family. It is expressed mainly in the retina. Mouse studies suggested that this gene is involved in development of retinal progenitors during embryogenesis, and that its activity is restricted to mature photoreceptors after birth. Mutations in this gene cause autosomal recessive retinitis pigmentosa-28. Alternatively spliced transcript variants have been identified.[provided by RefSeq, Jan 2011]

FAM161A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FAM161A	NM_001201543.2 linkuse as main transcript	c.*1136G>T		3_prime_UTR_variant	7/7	ENST00000404929.6	NP_001188472.1

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FAM161A	ENST00000404929.6 linkuse as main transcript	c.*1136G>T	3_prime_UTR_variant	7/7	1	NM_001201543.2	ENSP00000385158	P1	Q3B820-3
FAM161A	ENST00000405894.3 linkuse as main transcript	c.*1136G>T	3_prime_UTR_variant	6/6	1		ENSP00000385893		Q3B820-1
FAM161A	ENST00000456262.5 linkuse as main transcript	c.*2634G>T	3_prime_UTR_variant, NMD_transcript_variant	6/6	1		ENSP00000396105
FAM161A	ENST00000418113.5 linkuse as main transcript	c.*1759G>T	3_prime_UTR_variant, NMD_transcript_variant	8/8	5		ENSP00000416861

Frequencies

GnomAD3 genomes

AF:

0.000822

AC:

125

AN:

152066

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000217

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000852

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00150

Gnomad OTH

AF:

0.000480

GnomAD3 exomes

AF:

0.000704

AC:

AN:

130622

Hom.:

AF XY:

0.000799

AC XY:

AN XY:

71302

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000903

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000134

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00121

Gnomad OTH exome

AF:

0.00175

GnomAD4 exome

AF:

0.000888

AC:

268

AN:

301926

Hom.:

Cov.:

AF XY:

0.000941

AC XY:

162

AN XY:

172066

show subpopulations

Gnomad4 AFR exome

AF:

0.000117

Gnomad4 AMR exome

AF:

0.00117

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000117

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00139

Gnomad4 OTH exome

AF:

0.000356

GnomAD4 genome

AF:

0.000821

AC:

125

AN:

152184

Hom.:

Cov.:

AF XY:

0.000699

AC XY:

AN XY:

74406

show subpopulations

Gnomad4 AFR

AF:

0.000217

Gnomad4 AMR

AF:

0.000851

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00150

Gnomad4 OTH

AF:

0.000475

Alfa

AF:

0.000682

Hom.:

Bravo

AF:

0.000861

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Retinitis pigmentosa

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

1.3

DANN

Benign

0.50

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over